beta-Lapachone induced cell death in human hepatoma (HepA2) cells.
In present study we studied the cytotoxic effects of beta-lapachone, a potent anticancer drug, on the human hepatoma cell line (HepA2) under serum-free condition. Most cells died after 2 microM beta-lapachone addition at 48 hours. No apoptotic characteristics of DNA ladder was documented by agarose DNA electrophoresis. The blockage of cell cycle at S phase and unscheduled DNA synthesis were demonstrated by flow cytometric analysis and anti-bromodeoxyuridine immunocytochemistry. Ultrastructural observation showed that the swollen mitochondria, dilatation and vesiculation of rER and proliferation of peroxisome-like granules appeared within the cytoplasm of HepA2 cells following drug treatment. Using enzyme cytochemistry, both peroxidase and acid phosphatase activities but not catalase activity were localised in these peroxisome-like granules. Therefore, these results suggested that (a) beta-lapachone has a novel cytotoxic effect on human hepatoma cell; (2) beta-lapachone induces the interruption of the cell cycle and unscheduled DNA synthesis in HepA2 cells; and (3) beta-lapachone promotes the proliferation of peroxisome-like granules containing peroxidase and acid phosphatase activities without evidence of catalase activity in hepatoma cell line.
Lai
C C
CC
Institute of Anatomy, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Liu
T J
TJ
Ho
L K
LK
Don
M J
MJ
Chau
Y P
YP
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D003594:Cytoplasmic Granules / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008830:Microbodies / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D009285:Naphthoquinones; C014638:beta-lapachone